Nicotinic Modulation of Glutamate and GABA Synaptic Transmission in Hippocampal Neurons
Abstract
Although the hippocampus expresses nicotinic acetylcholine receptors (nAChRs) and receives cholinergic innervation, the functional roles of these receptors are not completely understood. Our results indicated that presynaptic nAChRs mediated a calcium influx that enhanced the release of both glutamate and GABA. Fura-2 detection of calcium in single mossy fiber presynaptic terminals indicated that nAChRs directly mediated a calcium influx. In hippocampal neurons in primary culture, both spontaneous vesicular release and evoked release of glutamate and GABA were enhanced by nicotine. The nicotinic current displayed rapid desensitization kinetics, and the response to nicotine was inhibited by alpha-bungarotoxin and methyllcaconitine, suggesting that nAChRs containing the alpha 7 subunit mediated the effect. Modulation of synaptic activity by presynaptic calcium influx may represent a physiological role of acetylcholine in the brain, as well as a mechanism of action of nicotine.
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A role for ACh in regulation of hippocampal excitability through presynaptic release of glutamate and GABA has been well-characterized.
“and a role for ACh in regulation of hippocampal excitability through presynaptic release of glutamate and GABA has also been well-characterized (Alkondon et al., 1997; Freund et al., 1988; Radcliffe et al., 1999).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Radcliffe et al., 1999
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- Authors
- RADCLIFFE, K. A., FISHER, J. L., GRAY, R., & DANI, J. A.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- DANI, JOHN A.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 1999-04
- Volume
- 868
- Issue
- 1
- Pages
- 591-610
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W2139254199
- Cited by
- 205
- References
- 61
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 8 · 2017: 7 · 2016: 5 · 2015: 8 · 2014: 10 · 2013: 7 · 2012: 7
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotinic acetylcholine receptors, alpha7 nicotinic acetylcholine receptor, glutamate release, GABA release, presynaptic calcium influx, mossy fiber terminals, synaptic transmission, nicotine, acetylcholine, receptor desensitization, alpha-bungarotoxin, methyllycaconitine, hippocampus
- MeSH terms
- Acetylcholine, Animals, Bungarotoxins, Cell Line, Electrophysiology, gamma-Aminobutyric Acid, Hippocampus, Synaptic Transmission, Neurons, Nicotine, Plants, Toxic, Receptors, Nicotinic, Nicotiana, Glutamic Acid, Rats
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